Currently, the majority of newly marketed biotherapeutics consist in recombinant proteins. Nevertheless, an important part of these proteins of human origin are associated to side effects relative to immunogenicity.
Glycosylation and more particularly sialylation are modifications which affect both the production and activity of proteins, and participate to proper recognition of proteins by the immune system. These post-translational modifications are also involved in the solubility, stability, protein-protein and cell-cell interactions as well as in the circulatory life span of proteins.
Thus, there is a crucial need to produce recombinant proteins having a glycosylation and a sialylation pattern as similar as possible to a human native protein for developing proteins for medical use. It is worth noting that at the present time, the vast majority (>75%) of recombinant proteins are produced using mammalian non-human expression systems and many of them display undesired immunogenicity side effects and more than often short half-lives. Particularly, current recombinant proteins are particularly insufficiently sialylated and none contain 6-linked sialic acid, which is the typical mode of glycosylation in human blood
It is therefore widely admitted that expression systems used for producing proteins drugs request major improvements to obtain recombinant proteins having a glycosylation and more especially sialylation pattern similar to human native proteins.